Intravenous injection is currently used as a means for the administrating protein and peptide drugs such as insulin, vasopressin and the like. With the increasing popularity of these protein and peptide drugs, attempts have been made to develop more simple means for their administration, such as oral, percutaneous, nasal, suppository and the like administration means. In particular, oral administration has been examined from various angles as the most common means. However, the bioavailability of protein and peptide drugs is extremely poor when they are administered orally, because these drugs are easily decomposed and inactivated by the enzymes in the small intestine.
As a result, attempts have been made to improve the bioavailability of these protein and peptide drugs by making these drugs into pharmaceutical preparations in such a manner that these drugs are selectively released in the large intestine where digestive enzymes are scarcely present.
For example, an enteric coated preparation has been developed which releases its drug contents due to melting of the coat when exposed to an increased pH. In some cases, however, such a preparation is decomposed in an upper portion of the small intestines, or is excreted without releasing its drug contents, because its decomposition is sensitive to intradiurnal changes in the pH in digestive tracts and diet.
As another type of large intestine-selective drug release preparations, attempts have been made to apply certain types of polymers which are selectively decomposed in the large intestine by the specific activity of enzymes secreted by bacteria in the large intestine. A large variety of anaerobic bacteria inhabit the large intestine and secrete various types of enzymes which are different from the human digestive enzymes. For example, an enzyme which is capable of reducing an azo group into its corresponding amino group is known to be a bacterial enzyme. Polymers containing aromatic azo groups which are hydrolyzed by the azo-reducing bacterial enzyme have been disclosed, for instance, in U.S. Pat. No. 4,663,308 and EP-A-398472 and CA-A-2012469 corresponding to JP-A-3-7718 (the term "JP-A" as used herein means an "unexamined published Japanese patent application"). The means described above, however, have the disadvantages that the polymers have poor coat formability and low solubility, and the azo group is carcinogenic.